Advanced squamous cell carcinomas of the head and neck or esophagus have a very poor five-year survival despite aggressive local treatment with surgery, radiotherapy or both. Many such patients die of metastatic disease. Therefore, a pilot trial of aggressive combination chemotherapy is warranted to determine if an improved response rate or survival can be obtained. Bleomycin, cis-platinum II with hydration, and high-dose methotrexate with citrovorum rescue are agents with activity in these tumors. Thirty-three patients were treated with combinations of these agents. Twenty-six received a three-drug combination and 7 patients received only DDP and bleomycin. Twenty-six received a three-drug combination and 7 patients received only DDP and bleomycin. There was a 73 percent response rate in previously untreated patients with 4 complete and 12 partial responses, and a 55 percent response rate in previously treated patients, all PR's. Duration of response to a single course of chemotherapy is 8-12 weeks. Toxicity includes vomiting, alopecia, leukopenia, thrombocytopenia, mucositis and elevated serum creatinine. There were 2 drug-related deaths. Among the 22 responders, 12 had surgery, 5 had subsequent radiotherapy. Of the eleven patients who failed therapy, 3 had surgery and 1 had radiotherapy. Twelve patients received no local therapy. Six patients with advanced esophageal carcinoma were treated with this combination, and it is too early to develop meaningful response or survival data.